The misfolding and aggregation of specific proteins is an early and obligatory event in many of the age-related neurodegenerative diseases of humans. The initial cause of this pathogenic cascade and the means whereby disease spreads through the nervous system, remain uncertain. A recent surge of research, first instigated by pathologic similarities between prion disease and Alzheimer s disease, increasingly implicates the conversion of disease-specific proteins into an aggregate-prone b-sheet-rich state as the prime mover of the neurodegenerative process. This prion-like corruptive protein templating or seeding now characterizes such clinically and etiologically diverse neurological disorders as Alzheimers disease, Parkinson s disease, Huntington s disease, amyotrophic lateral sclerosis, and frontotemporal lobar degeneration. Understanding the misfolding, aggregation, trafficking and pathogenicity of the affected proteins could therefore reveal universal pathomechanistic principles for some of the most devastating and intractable human brain disorders. It is time to accept that the prion concept is no longer confined to prionoses but is a promising concept for the understanding and treatment of a remarkable variety of diseases that afflict primarily our aging society. "

This volume presents key topics of current interest with regard to several pathophysiological conditions including (a) the basic and clinical aspects of bradykinin receptor antagonists, (b) the kallikrein-kinin pathways in hypertension and diabetes, (c) tissue kallikrein-kinin therapy for hypertension and organ damage, (d) the renal (tissue) kallikrein-kinin system in the kidney and novel potential drugs for salt-sensitive hypertension, (e) the kallikrein-kinin system in diabetes retinopathy and (f) genetic manipulation and genetic variation of the kallikrein-kinin system and their impacts on cardiovascular and renal disease. Written by internationally reputed scientists, the book provides an essential overview of the latest developments in the field of kinin research, making it a valuable asset for endocrinologists, nephrologists, cardiologists, pharmacologists, physiologists, ophthalmologists and rheumatologists. Furthermore, it is also intended for postgraduate students in the fields of medicine, pharmacy, physiology and pharmacology and those working at research organizations.

Dr. Spitzer has created an issue devoted to the evidence-based pharmacologic care of the neonate. The issue opens with an important article on? A Quality Improvement Approach to Modifying Medication Use in the NICU. The expert authors he has secured have contributed articles in the areas of therapeutic drug monitoring, off-label use of medications in the NICU, antenatal and post-natal corticosteroids, antibiotics, antifungals, and antivirals, as well as bronchodilators and nitric oxide. Other articles also present evidence-based use of oxygen, dopamine, anesthetics and analgesics, and erythropoetin.

"Biotransformation of Pesticides" is an updated, "one-stop" resource for academic, industry and regulatory scientists involved in research and regulatory activities related to pesticide biotransformation and human health. This book provides anin depth look at how pesticides are biotransformed, which is essential to understanding exposure, dose, toxicity and health risks. This essential reference contains the biotransformation of pesticides from uptake to excretion, including toxicokinetics and emphasizes metabolism in non-target species, including experimental animals and humans.
Includes four new chapters and expanded material on pesticide biotransformation and disposition, an active area of pesticide toxicology that is becoming increasingly important for human health risk assessment

Offers a practical and portable guide covering the most up-to-date research results on metabolic transformations of pesticides

Provides scientists and regulatory researchers with the information they need to conduct accurate risk assessments and make informed decisions on which exposures to study further in human populations "

Topics in this issue?include: Targeting IGF-1R; Tyrosine Kinase Inhibitors in Lung Cancer; Targeting mTOR; Targeting Hedgehog; Mitotic Inhibitors; Topoisomerase I Inhibitors; and New Strategies and Drugs Inhibiting Folate Pathways.

Implantable cardioverter-defibrillators (ICDs) are electronic devices installed in the chest to prevent sudden death caused by abnormally fast heart rhythms. Cardiac electrophysiologists are the physicians usually responsible for implanting and maintaining these devices.? The technology for ICDs is rapidly evolving, and the articles in this issue will help electrophysiologists to keep up to date with the current generation of ICDs, including selection of patients who are appropriate for the device, monitoring patients after the device is implanted, and troubleshooting problems with the device.

Fluorine chemistry is an expanding area of research that is attracting international interest, due to the impact of fluorine in drug discovery and in clinical and molecular imaging (e.g. PET, MRI). Many researchers and academics are entering this area of research, while scientists in industrial and clinical environments are also indirectly exposed to fluorine chemistry through the use of fluorinated compounds for imaging.This book provides an overview of the impact that fluorine has made in the life sciences. In the first section, the emphasis is on how fluorine substitution of amino acids, peptides, nucleobases and carbohydrates can provide invaluable information at a molecular level. The following chapters provide answers to the key questions posed on the importance of fluorine in drug discovery and clinical applications. For examples, the reader will discover how fluorine has found its place as a key element improving drug efficacy, with reference to some of the best-selling drugs on the market. Finally, a thorough review on the design, synthesis and use of 18F-radiotracers for positron emission tomography is provided, and this is complemented with a discussion on how 19F NMR has advanced molecular and clinical imaging.

"Annual Reports in Medicinal Chemistry "provides timely and critical reviews of important topics in medicinal chemistry together with an emphasis on emerging topics in the biological sciences, which are expected to provide the basis for entirely new future therapies.

Although antiviral drugs have been successfully developed for some viral diseases, there remains a clear, unmet medical need to develop novel antiviral agents for the control and management of many viruses that currently have no or limited treatment options as well as a need to overcome the limitations associated with the existing antiviral drugs, such as adverse effects and emergence of drug-resistant mutations. The second edition of Antiviral Methods and Protocols features: All chapters are new and written by experts in the field, reflecting the major recent technical advances in antiviral research and discovery. This edition focuses on many important human viruses, such as human immunodeficiency virus type 1 (HIV-1), hepatitis viruses (hepatitis B and C viruses), herpes viruses, human respiratory syncytial virus (RSV), and influenza virus, while also featuring some important emerging viruses, such as dengue virus, West Nile virus, and chikungunya virus. As a volume in the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Antiviral Methods and Protocols, Second Edition will serve as an excellent laboratory reference for pharmaceutical and academic biologists, medicinal chemists, and pharmacologists as well as for virologists in the field of antiviral research and drug discovery.

This volume of Methods in Enzymology looks at Protein Engineering for Therapeutics. The chapters providean invaluable resource for academics, researchers and students alike. With an international board of authors, this volume is split into sections that cover subjects such as Antibodies, Protein conjugates, Peptides, Enzymes and Scaffolds
Chapters providean invaluable resource for academics, researchers and students alike. Iinternational board of authors. This volume is split into sections that cover subjects such as Antibodies, Protein conjugates, Peptides, Enzymes and Scaffolds"

A comprehensive review of toxicology for the small animal practitioner Guest editors Safdar Khan and Stephen Hooser present articles on trends of animal poisoning cases in the USA, use of lipid emulsions, epidemiology of mushroom poisoning cases, toxicology of ADHD drugs, toxicology of human NSAIDS, diagnostic toxicology with emphasis on how to investigate or what to do in food-related outbreaks, toxicology of avermectins (ivermectins, moxidectin, doramectin, selamectin), rodenticides toxicosis, include difethiolone, toxicology of newer pesticides, toxicology of explosives, recently recognized nephrotoxic agents/toxicants, calcium channel blocker toxicosis, adverse effects, and more

"Omics for Personalized Medicine" will give to its prospective readers the insight of both the current developments and the future potential of personalized medicine. The book brings into light how the pharmacogenomics and omics technologies are bringing a revolution in transforming the medicine and the health care sector for the better. Students of biomedical research and medicine along with medical professionals will benefit tremendously from the book by gaining from the diverse fields of knowledge of new age personalized medicine presented in the highly detailed chapters of the book. The book chapters are divided into two sections for convenient reading with the first section covering the general aspects of pharmaocogenomic technology that includes latest research and development in omics technologies. The first section also highlights the role of omics in modern clinical trials and even discusses the ethical consideration in pharmocogenomics. The second section is focusing on the development of personalized medicine in several areas of human health. The topics covered range from metabolic and neurological disorders to non-communicable as well as infectious diseases, and even explores the role of pharmacogenomics in cell therapy and transplantation technology. Thirty-four chapters of the book cover several aspects of pharmacogenomics and personalized medicine and have taken into consideration the varied interest of the readers from different fields of biomedical research and medicine. Advent of pharmacogenomics is the future of modern medicine, which has resulted from culmination of decades of research and now is showing the way forward. The book is an honest endeavour of researchers from all over the world to disseminate the latest knowledge and knowhow in personalized medicine to the community health researchers in particular and the educated public in general.

This issue of Neurologic Clinics addresses the neurologic consequences of exposure to environmental toxins.

The Side Effects of Drugs Annual was first published in 1977. It has been published continuously since then, as a yearly update to the encyclopaedic volume Meyler's Side Effects of Drugs. Each new Annual provides clinicians and medical investigators with a reliable and critical yearly survey of new data and trends in the area of Adverse Drug Reactions and Interactions. An international team of specialists have contributed to the Annuals by selecting from each year's publications all that is truly new and informative, by critically interpreting it, and by pointing out whatever is misleading. The use of the book is enhanced by separate indexes, allowing the reader to enter the text via the drug name, adverse effect, or drug interaction. Special features of the Annuals are the Side Effects of Drugs Essay, usually written by a guest author, and the special reviews: short articles, within the different chapters, that give extra attention to topics of current interest. The Essay in Annual 27 is entitled 'The General Practice Research Database' (by Dr. H. Jick) and there is a Historical Essay entitled 'Louis Lewin - Meyler's Predecessor' (by Dr. J.K. Aronson). The special reviews in this volume include, among others: The effects of NSAIDs on blood pressure Risks of inhaled corticosteroids in children Leukotriene receptor antagonists and Churg-Strauss syndrome Amiodarone and thyroid disease Surveillance of adverse events following immunization Smallpox vaccination Safety aspects of folic acid Inhibitors of topoisomerase I and topoisomerase II Liver damage from kava kava

The objective of this volume is to give an overview of the present state of the art of pediatric clinical pharmacology including developmental physiology, pediatric-specific pathology, special tools and methods for development of drugs for children (assessment of efficacy, toxicity, long-term safety etc.) as well as regulatory and ethical knowledge and skills. In the future, structural and educational changes have to lead back to a closer cooperation and interaction of pediatrics with (clinical) pharmacology and pharmacy.

Aromatase Inhibitors (AIs) treat postmenopausal estrogen receptor positive tumours, which constitute the majority of breast cancer patients. This comprehensive volume brings together the current knowledge from different relevant areas, including molecular mechanisms and translational aspects of drug resistance in AIs. Topics covered include research, experimental , and clinical data specifically focused on AI resistance in breast cancer. The volume will include three sections. The first section covers general knowledge about aromatase inhibitors, including regulation of aromatase genes, and structure and function of aromatase protein. The second section provides the detailed mechanisms of resistance to AIs, while the third section explores prediction of resistance and potential strategies to overcome resistance. Breast cancer is the most common female cancer and AIs significantly improve treatments outcomes compatibly to previously used endocrine treatments. However 10-15% of post-operative patients develop a relapse during adjuvant treatment with AIs; about 25-50% of the patients do not respond to AIs in neo-adjuvant or metastatic setting, and the majority of metastatic patients who initially respond develop resistance within 3 years. There is an important need to understand these mechanisms of resistance in order to develop methods of preventing or overcoming the resistance to AIs, which will ensure a more successful outcome in treating breast cancer.

Pharmacology in Drug Discovery: Understanding Drug Response is designed for all students, recent graduates, and new researchers in the pharmaceutical and biotechnology industries who need to interpret change in physiology induced by a chemical substance. Physiological systems customize chemical signal input to their own needs; therefore the same drug can have different effects in different physiological systems. The field of pharmacology is unique in that it furnishes the tools to analyze these different behaviors and traces them to their root cause. This enables predictions of drug behavior to be made in all systems, an invaluable tool for drug discovery because almost all drugs are developed in test systems far removed from the therapeutic one.
This valuable resource provides simple explanations of the ways in which biological systems use basic biochemical mechanisms to produce fine chemical control of physiology, allowing for more informed predictions of drug effects in all systems and forming the basis of the drug-discovery process. Chapters follow a logical progression on how to characterize the pharmacology of any given molecule, and include important terminology, chapter summaries, references, and review questions to aid the reader in understanding and retention of the material.
Enables the reader to interpret drug dose-response data and make mechanistic inferences at the molecular levelBridges the gap between biochemistry and therapeutic medicineChapters include key topics such as drug affinity and efficacy, enzymes as drug targets, in vivo pharmacology, safety pharmacology, and more"

G Protein-Coupled Receptor Genetics: Research and Methods in the Post-Genomic Era features practical techniques inspired by the fast moving GPCR field. From powerful bioinformatic tools tracing the evolution of GPCRs, to methods for the cellular transfection of engineered viruses containing GPCRs, to optogenetic techniques that produce light-activated GPCRs in live mice, what was once science fiction is now science fact. This detailed volume includes sections covering genetic mechanisms, a genetic toolbox for GPCR discovery, as well as genetic aspects of G protein-coupled receptors in health and medicine. Written for the Methods in Pharmacology and Toxicology series, this book contains the kind of key implementation advice that encourages successful results in the lab. Authoritative and easy to use, G Protein-Coupled Receptor Genetics: Research and Methods in the Post-Genomic Era serves as an ideal guide for researchers aiming to continue our progress in this dynamic and exciting area of study.

Metastatic disease is the most lethal aspect of human malignancies, making the understanding and continued research of the process of metastasis a crucial step in treating cancer. The proposed book, entitled "Experimental and Clinical Metastasis: A Comprehensive Review" aims to provide a clear and extensive review of the clinical and experimental implications of metastatic disease. This work focuses on recent contributions to the field of metastasis, and will highlight crucial findings in the molecular understanding of disseminated disease as well as standard and personalized medicine currently being investigated in the clinic. Topics will include, among many, gene properties of metastatic cells, molecular mechanisms of tumour growth and spread, animal models of metastasis, and clinical implications, markers and treatment for metastatic disease. With the participation of worldwide experts in the field of oncology, from major academic and government centres, this book will provide a leading manual for the study of the metastatic process, from benchside science to bedside care. In this light, the proposed book will facilitate classroom learning for both medical and graduate students, as well as serve as a tool for physicians and researchers interested in the metastatic process. In addition, this book will include the latest advances in basic science as well as leading technologies and theories of targeting metastatic cells. Most importantly, not only will basic and clinical aspects be discussed, but furthermore, the translational aspect of research in metastatic diseases will be emphasized.

Within recent years pharmaceuticals have come into focus as contaminants of the environment (see for example Kummerer, K. editor: Pharmaceuticals in the Environment). At the same time the issue of sustainable chemistry gained momentum. Bringing both together would result in sustainable pharmacy. Sustainable pharmacy is a totally new issue and approach. It addresses environmental, economical and social aspects of pharmacy. In the present stage the focus will be on environmental issues along the whole lifecycle of a pharmaceutical entity. That is dealing with resources and energy input but also with waste issues for example during the synthesis and production of an active pharmaceutical ingredient. Furthermore, it would also look on the compounds themselves and will aim to improve the degradability of the compounds after their use in the environment to reduce the environmental risk caused by pharmaceuticals in the environment. Another issue is the people using pharmaceuticals such as pharmacists, medical doctors and patients. How can they contribute to more efficient use of pharmaceuticals with less environmental burden and less risk for drinking water. The book "Sustainable Pharmacy" will address all these issues and will be the first one dealing with this important topic.